Lacosamide chemically known as (R)-N-benzyl-2-acetamido-3-methoxy-propionamideor (2R)-2-(Acetylamino)-3-methoxy-N-(phenylmethyl)propanamide of Formula I is an amino acid derivative having analgesic and anticonvulsant property.

Lacosamide was developed by UCB Pharma for the adjunctive treatment of partial-onset seizures. It is marketed under the trade name Vimpat and was approved by US FDA as an adjunctive therapy for partial-onset seizures in October 2008.
Lacosamide has been disclosed for the first time in the U.S. Pat. No. 5,773,475 by Research Corporation Technologies. According to this patent, lacosamide is prepared in three different methods. The first two methods do not involve the protection of starting material that is D-Serine is used which is converted to methyl ester followed by the reaction with benzylamine to obtain the benzylamide derivative which acetylated with acetic anhydride to obtain N-acetyl derivative. Methylation is employed with methyl iodide in the presence of silver oxide which results in Lacosamide along with the racemized product of Lacosamide.
The third method employs Cbz protected D-serine as a starting material which methylated followed by benzylation, deprotection and acetylation to obtain lacosamide. These routes are commercially not viable due to low yield since O-methylation of N-protected D-serine results in partial racemization which reduces the yield. Further the removal of S-enantiomer is difficult during production of (R)-2-acetamido-N-benzyl-3-methoxypropionamide.
An alternate method for the synthesis of Lacosamide is described in the application WO2006037574 which discloses O-methylation of N-Boc protected D-serine by employing n-Butyl lithium and dimethyl sulphate which reduces the formation of other isomer.
Another alternate method for the synthesis of Lacosamide is described in the application US20090143472 wherein the starting material employed is benzylamine amidation of N-trityl D-serine, further O-methylation, de-tritylation followed by acetylation to obtain Lacosamide. Another method involves O-methylation of N-trityl D-Serine, benzylamine amidation, detritylation and finally acetylation to obtain lacosamide.
An alternate method for the synthesis of Lacosamide is described in the application WO2010052011 wherein the racemic Lacosamide resolution to afforded R-enantiomer of Lacosamide by employing chiral chromatography.
Therefore, the present invention provides a novel process for the preparation of Lacosamide by avoiding costly reagents and the chromatography technique.